pneumonia in adult patients in Turkey;
a multicentric, cross-sectional study
İftihar KÖKSAL1, Tevfik ÖZLÜ2, Özlem BAYRAKTAR1, Gürdal YILMAZ1, Yılmaz BÜLBÜL2,
Funda ÖZTUNA2, Rahmet ÇAYLAN1, Kemalettin AYDIN1, Nurgün SUCU1, *TUCAP Çalışma Grubu3
1Karadeniz Teknik Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Trabzon,
2 Karadeniz Teknik Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları Anabilim Dalı, Trabzon,
3 Akdeniz Üniversitesi Tıp Fakültesi, Antalya/Ankara Üniversitesi Tıp Fakültesi, Ankara/Dicle Üniversitesi Tıp Fakültesi, Diyarbakır/Erciyes Üniversitesi Tıp Fakültesi, Kayseri/Fırat Üniversitesi Tıp Fakültesi, Elazığ/Pamukkale Üniversitesi Tıp Fakültesi, Denizli/Uludağ Üniversitesi Tıp Fakültesi, Bursa.
*TUCAP (Türkiye Toplum Kökenli Pnömoni Çalışma Grubu) Üyeleri
Dilara İnan Özcan, Akdeniz Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Antal- ya/Candan Öğüş, Akdeniz Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları ve Tüberküloz Anabilim Dalı, Antalya/
Emin Tekeli, Ankara Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Ankara/
Akın Kaya, Ankara Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları ve Tüberküloz Anabilim Dalı, Ankara/Celal Ayaz, Dicle Üni- versitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Diyarbakır/Canan Eren Dağlı, Dicle Üniver- sitesi Tıp Fakültesi, Göğüs Hastalıkları ve Tüberküloz Anabilim Dalı, Diyarbakır/Orhan Yıldız, Erciyes Üniversitesi Tıp Fakülte- si, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Kayseri/Fatma Sema Oymak, Erciyes Üniversitesi Tıp Fakülte- si, Göğüs Hastalıkları ve Tüberküloz Anabilim Dalı, Kayseri/Ahmet Kalkan, Fırat Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalık- ları ve Klinik Mikrobiyoloji Anabilim Dalı, Elazığ/Mehmet Hamdi Muz, Fırat Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları ve Tü- berküloz Anabilim Dalı, Elazığ/Hüseyin Turgut, Pamukkale Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobi- yoloji Anabilim Dalı, Denizli/Fatma Fişekçi, Pamukkale Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları ve Tüberküloz Anabilim Dalı, Denizli/Yasemin Heper, Uludağ Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, Bur- sa/Esra Uzaslan, Uludağ Üniversitesi Tıp Fakültesi, Göğüs Hastalıkları ve Tüberküloz Anabilim Dalı, Bursa.
ÖZET
Türkiye’de erişkin hastalarda toplum kökenli pnömonilerde etyolojik ajanlar;
çok merkezli, kesitsel çalışma
Bu kesitsel çalışma öncesinde antibiyotik tedavisi almayan erişkin hastalarda toplum kökenli pnömoniler (TKP)’in etyolo- jisinin araştırılması için tasarlandı. Çalışmaya alınan 218 hastanın 137 (%62.8)’sinde etyolojik ajan tespit edildi. En sık tes- pit edilen ajanlar Streptococcus pneumoniae (%14.7), Mycoplasma pneumoniae (%13.8) ve respiratuar sinsityal virüs (%10.1) idi. Olguların %50.9’unda tek patojen, %11.9’unda çoklu patojen belirlendi. Olguların %35.8’inde tipik patojenler,
Yazışma Adresi (Address for Correspondence):
Dr. İftihar KÖKSAL, Karadeniz Teknik Üniversitesi Tıp Fakültesi, İnfeksiyon Hastalıkları ve Klinik Mikrobiyoloji Anabilim Dalı, TRABZON - TURKEY
e-mail: iftihar@yahoo.com
Despite recent advances in diagnosis, treatment and vaccination, community-acquired pneumo- nia (CAP) is still one of the most common infec- tious diseases worldwide. It remains a major ca-
use of morbidity and mortality, and contributes significantly to excessive consumption of he- althcare resources and related costs (1-4). In Turkey, a pneumonia rank 15th among the 20
%20.2’sinde atipik patojenler, %20.6’sında ise viral patojenler belirlendi. Altta yatan hastalık olarak hastaların %42.7’sinde kronik obstrüktif akciğer hastalığı vardı. S. pneumoniae TKP’li erişkin hastalarda en yaygın patojendi. Atipik patojenler 65 yaşın altında daha yaygındı. M. pneumoniae bu yaş grubunda en sık etkendi. Çalışmamız, Türkiye’de TKP’li hastalarda başlangıç antibiyotik tedavisinin, S. pneumoniae ve M. pneumoniae’yı kapsaması gerektiğini göstermektedir.
Anahtar Kelimeler: Toplum kökenli pnömoni, risk faktörleri, pnömoni etyolojisi.
SUMMARY
Etiological agents of community-acquired pneumonia in adult patients in Turkey;
a multicentric, cross-sectional study
İftihar KÖKSAL1, Tevfik ÖZLÜ2, Özlem BAYRAKTAR1, Gürdal YILMAZ1, Yılmaz BÜLBÜL2, Funda ÖZTUNA2, Rahmet ÇAYLAN1, Kemalettin AYDIN1, Nurgün SUCU1, *TUCAP Study Group3
1 Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.
2Department of Chest Diseases, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey.
3Faculty of Medicine Akdeniz University, Antalya/Faculty of Medicine Ankara University, Ankara/ Faculty of Medicine Dic- le University, Diyarbakir/Faculty of Medicine Erciyes University, Kayseri/Faculty of Medicine Firat University, Elazig/Fa- culty of Medicine Pamukkale University, Denizli/Faculty of Medicine Uludag University, Bursa, Turkey.
* TUCAP (Turkish Community-Acquired Pneumonia Study Group) Members
Dilara İnan Özcan, Department of Infectious Diseases and Clinical Microbiology, Akdeniz University Medical Faculty, Antalya/Can- dan Öğüş, Department of Chest Diseases and Tuberculosis, Akdeniz University Medical Faculty, Antalya/Emin Tekeli, Department of Infectious Diseases and Clinical Microbiology, Ankara University Medical Faculty, Ankara/Akın Kaya, Department of Chest Di- seases and Tuberculosis, Ankara University Medical Faculty, Ankara/Celal Ayaz, Department of Infectious Diseases and Clinical Microbiology, Dicle University Medical Faculty, Diyarbakir/Canan Eren Dağlı, Department of Chest Diseases and Tuberculosis, Dicle University Medical Faculty, Diyarbakir/Orhan Yıldız, Department of Infectious Diseases and Clinical Microbiology, Erciyes University Medical Faculty, Kayseri/Fatma Sema Oymak, Department of Chest Diseases and Tuberculosis, Erciyes University Me- dical Faculty, Kayseri/Ahmet Kalkan, Department of Infectious Diseases and Clinical Microbiology, Firat University Medical Fa- culty, Elazig/Mehmet Hamdi Muz, Department of Chest Diseases and Tuberculosis, Firat University Medical Faculty, Elazig/Hüse- yin Turgut, Department of Infectious Diseases and Clinical Microbiology, Pamukkale University Medical Faculty, Denizli/Fatma Fi- şekçi, Department of Chest Diseases and Tuberculosis, Pamukkale University Medical Faculty, Denizli/Yasemin Heper, Department of Infectious Diseases and Clinical Microbiology, Uludag University Medical Faculty, Bursa/Esra Uzaslan, Department of Chest Di- seases and Tuberculosis, Uludag University Medical Faculty, Bursa, Turkey.
This cross-sectional study was intended to investigate the etiology of community-acquired pneumonia (CAP) in adult patients receiving no prior antibiotic therapy. Etiological agents were identified in 137 (62.8%) of 218 patients, the most frequent being Streptococcus pneumoniae (14.7%), Mycoplasma pneumoniae (13.8%) and respiratory syncytial virus (10.1%). A single pathogen was detected in 50.9% of cases and mixed pathogens in 11.9%. Typical pathogens were de- termined in 35.8% of cases, atypical pathogens in 20.2% and viral pathogens in 20.6%. Chronic obstructive pulmonary disease was a common (42.7%) comorbidity. S. pneumoniae was the most common pathogen in adult patients with CAP. Atypical pathogens were more common in patients < 65 years old, M. pneumoniae being the most common in this age group. Our results suggest that initial empiric antibiotic treatment in patients with CAP should cover S. pneumoni- ae and M. pneumoniae in Turkey.
Key Words: Community-acquired pneumonia, risk factors, etiology of pneumonia.
most frequent acute and chronic diseases and is the 5th leading cause of death (5). Despite the fact that a great number of microbial agents can cause CAP, often no specific etiological diagno- sis is established at the time of initial treatment, and antimicrobial therapy is usually performed using an empiric approach in such patients (2).
In order to administer micro-organism-guided treatment, it is necessary to determine the ca- usative pathogens of CAP.
The etiological agents of CAP may vary accor- ding to geographic area and patients´ underlying risk factors. Decisions on proper empiric antibi- otic therapy will therefore depend on prospecti- ve epidemiological studies (3). Surveillance stu- dies constitute an important tool for determining local and regional susceptibility patterns and gu- iding empiric antimicrobial therapy (6). The ma- jority of studies that have investigated the mic- robial causes of CAP have been carried out with patients admitted to hospital. Only a few studies have been undertaken to determine the etiology of CAP in the ambulatory patient (7).
Only a few studies of the etiology of CAP have been performed in adult patients in an ambula- tory setting in Turkey (5,8-10). In this multicent- ric, cross-sectional study, we determined etiolo- gical agents of CAP in ambulatory adult patients in the country.
MATERIALS and METHODS Study Design
Eight university hospitals from different geog- raphical regions of Turkey between November 2003 and March 2005 were included in this mul- ticentric, cross-sectional study. In selecting cen- ters, the following features were sought: the abi- lity to represent different geographical areas, the ability to perform the investigative procedures in the study protocol in an optimal manner, and fa- cility in coordination.
A Turkish Community-Acquired Pneumonia (TU- CAP) Study Group was coordinated under the In- fectious Diseases and Clinical Microbiology and Chest Diseases and Tuberculosis departments of the Karadeniz Technical University Medical Fa- culty. TUCAP members belong to infectious dise-
ases and clinical microbiology departments or chest diseases and tuberculosis departments in the study centers. The study was approved by the Institutional Ethical Committee, and written infor- med consent was obtained from all patients or their legal representatives before enrolment.
Patients
The study population consisted of adult CAP pa- tients > 17 years old and who attended an out- patient clinic at one of the study centers. Pati- ents consisted of individuals living in urban as well as rural areas. All patients had clinical fe- atures and radiological findings compatible with CAP. CAP was defined as an acute illness asso- ciated with at least one of the following criteria;
fever (> 38°C) or hypothermia (< 36°C), new cough with or without sputum production, ple- uritic chest pain, dyspnea or altered breath so- und on auscultation, plus a chest radiograph showing an opacity or new infiltrate consistent with pneumonia (11). CURB 65 score was used to determine disease severity (12). Patients with a diagnosis of immunosuppressive disorder, tu- berculosis, health care associated pneumonia, aspiration pneumonia, antibiotic use in the last 48 hours, transferred from any health institution, hospitalization within the previous 2 weeks or pregnancy were excluded.
Demographic and clinical data were collected by an investigator using a standardized questionna- ire. In order to establish microbial etiology, spu- tum, nasopharyngeal aspirate, blood and urine samples were taken from the subjects. All samp- les were collected before the start of antibiotic therapy. Acute serum samples were collected on admission, and convalescent serum samples 2 and 4 weeks after initial diagnosis of CAP.
Microbiological Evaluation
Sputum and nasopharyngeal aspirate samples were investigated using Gram’s stain and then cultured. Only sputum samples with > 25 white blood cells and < 10 squamous cells/per low- magnification field (X10) were evaluated. Na- sopharyngeal aspirate samples were also inves- tigated for adenovirus, influenza A and B, para- influenza viruses and respiratory syncytial virus
(RSV) antigen employing a direct immunoflu- orescent technique using antigen-specific mo- noclonal antibody kits according to the manufac- turer’s instructions for the detection of respira- tory viruses (Argene; Biosoft, Varilhes, France).
In the acute stage of illness and 2-4 weeks later, serum samples were investigated for IgM and IgG antibodies for RSV, adenovirus, influenza virus A and B, parainfluenza viruses 1, 2, 3 and 4, Mycoplasma pneumoniae, Coxsackie virus type 7, Chlamydia pneumoniae, Legionella pneumop- hila serotypes 1 and 12, Bordetella pertussis and Bordetella parapertussis using an indirect immu- nofluorescent technique (Argene; Biosoft, Varil- hes, France). Chlamydia specific analyses were performed using a microimmunofluorescence technique (MIF) for IgG and IgM antibodies (MRL Diagnostics, IF 1200A, IF1200M, IF 1200G; Ca- lifornia/ABD). Urine samples were assayed for L.
pneumophila antigens by radioimmunoassay (Binax, Portland, Maine, USA).
Criteria for Etiological Diagnosis
The following criteria were used to determine etiology:
Isolation of pathogenic microorganisms (Strep- tococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and other bacteria, including gram-negative en- terobacteria and gram-positive bacteria) qualifi- ed sputum samples or nasopharyngeal aspirate samples;
Detection of adenovirus, influenza A and B and parainfluenza viruses and RSV antigens by direct immunofluorescence in nasopharyngeal aspirate;
For serological tests, a 4-fold rise in the anti- body titer in paired sera, or presence of IgM an- tibodies;
For C. pneumoniae: a 4-fold rise in IgG titer or presence of IgM antibodies (≥ 1/16);
Detection of L. pneumophila antigens in urine.
Cases that did not fulfil these diagnostic criteria were interpreted to be “No etiology determined”.
Statistical Analysis
The chi-square test was used. p< 0.05 was re- garded as statistically significant.
RESULTS
Two hundred ninety-two CAP patients were en- rolled, of whom 218 were eventually analyzed.
Seventy-four patients were excluded from analysis due to failure to obtain paired serum samples or to meet eligibility criteria, or else due to incomplete data. The mean age of en- rolled patients was 57.5 ± 17.6. Ninety-four pa- tients (43.1%) were older than 65. One hund- red forty-seven patients were male and 71 fe- male. All of patients had CURB-65 < 2. One hundred forty-two of the 218 patients (65.1%) had at least one comorbidity. The main demog- raphic characteristics of the patients were sum- marized Table 1.
An etiological diagnosis was established in 137 out of the 218 (62.8%) patients. A total of 167 pathogens were isolated from 137 patients. A single pathogen was detected in 111 (50.9%) cases and 2 or more pathogens in 26 (11.9%) cases. No microorganism was determined in 81 (37.2%) patients. Typical pathogens were pre- sent in 35.8% of patients, atypical pathogens in 20.2% and viral pathogens in 20.6% The 3 most frequent pathogens were S. pneumoniae (14.7%), M. pneumoniae (13.8%) and RSV (10.1%) (Table 2).
Table 1. The main demographic characteristics of patients with CAP.
Characteristics Mean ± SD, n (%)
Age (y) 57.5 ± 17.6
≥ 65 year 94 (43.1)
< 65 year 124 (56.9)
Gender
Male 147 (67.4)
Female 71 (32.6)
Underlying diseases
COPD 93 (42.7)
Hypertension 65 (29.8)
Congestive heart failure 21 (9.6) Diabetes mellitus 19 (8.7)
Bronchiectasis 4 (1.8)
Chronic renal failure 3 (1.4) CAP: Community-acquired pneumonia, COPD: Chronic obstructive pulmonary disease.
Two pathogens were identified in 22 (10.1%) of the 26 patients with mixed pathogens and 3 pat- hogens in 4 (1.8%) patients. The most frequent combinations were a bacterial pathogen plus a viral pathogen. S. pneumoniae was determined in 9 patients with mixed pathogens. H. influen- zae was the second most frequent bacteria in mixed infections, in all cases together with a vi- ral agent.
Chronic obstructive pulmonary disease (COPD) was the most frequent comorbid factor, occur- ring in 42.7% of patients (93 out of 218). Other comorbidities were hypertension (29.8%), con- gestive heart failure (9.6%) and diabetes melli- tus (8.7%). Seventy-eight pathogens were deter- mined in 51 COPD subjects. The 4 most com- mon pathogens were S. pneumoniae (27.4%), RSV (25.5%), H. influenzae (17.6%) and M. pne- umoniae (17.6%).
When the distribution of the microorganisms by age was evaluated, the most frequent pathogen in patients ≥ 65 was S. pneumoniae (17.0%), follo- wed by RSV (13.8%) and M. pneumoniae (8.5%).
In patients < 65, the most frequent agent was M.
pneumoniae (17.7%), followed by S. pneumoniae (12.9%), H. influenzae (7.3%) and RSV (7.3%).
Pneumonia caused by Streptococcus spp. and P.
aeruginosa was observed in individuals aged >
65, though these agents were not encountered in subjects aged < 65 (p= 0.016; p= 0.037). Pne- umonia due to atypical agents was greater in sub- jects aged < 65 (p= 0.034) (Table 3).
DISCUSSION
In this cross-sectional study conducted in Tur- key, we determined etiology in 62.8% of patients with CAP. Levels of determination of the causati- ve micro-organisms in CAP in the literature vary from 16% to 65% (13-27). In previous small stu- dies in Turkey, the levels of etiological agents in pneumonia have been reported as, variously, 21% and 45.5 % of patients with CAP (Table 4).
Differences among these studies may be ascri- bed to prior antibiotic use and different methodo- logies and laboratory techniques (17). In parti- cular, disparities in frequencies of viruses and atypical bacteria may be due to the use of diffe- rent diagnostic laboratory techniques. For example, when only serological diagnostic met- hods were used, virus and atypical bacteria were diagnosed in only 16% of patients with acute bronchitis, whereas when viral and bacterial cul- tures of nasopharyngeal aspirates and sputum were added to the serological diagnostics these levels increased to 29-40% (16). In our study, na- sopharyngeal aspirate, sputum, urine and serum samples were also investigated, etiology being determined in 62.8% of cases. This level would probably have been even higher if the molecular diagnostic method could have been used.
In our study, typical pneumonia agents were de- monstrated in 35.8% of patients, atypical pne- umonia agents in 20.2% and viral pneumonia agents in 20.6%. Mixed pneumonia agents were determined in 11.9% of patients. These propor- tions have been reported as 40%-54% for typical pathogens, 8%-63% for atypical pathogens and Table 2. Distribution of etiological agents in 218
patients with CAP.
Microorganism Number (%) Etiology determined 137 (62.8)
Typical pathogens 78 (35.8) [46.7]*
Streptococcus pneumoniae 32 (14.7) [19.2]*
Haemophilus influenzae 13 (6.0) [7.8]*
Klebsiella pneumoniae 8 (3.7) [4.8]*
Streptococcusspp. 5 (2.3) [3]*
Moraxella catarrhalis 5 (2.3) [3]*
Escherichia coli 4 (1.8) [2.4]*
Pseudomonas aeruginosa 4 (1.8) [2.4]*
Other gram-negative 4 (1.8) [2.4]*
Other gram-positive 3 (1.4) [1.8]*
Atypical pathogens 44 (20.2) [26.3]*
Mycoplasma pneumoniae 30 (13.8) [18]*
Chlamydia pneumoniae 9 (4.1) [5.4]*
Legionella pneumophila 5 (2.3) [3]*
Viral pathogens 45 (20.6) [26.9]*
Respiratory syncytial virus 22 (10.1) [13.2]*
Parainfluenzae virus 11 (5.0) [6.6]*
Influenzae virus 10 (4.6) [6]*
Coxackie virus 2 (0.9) [1.2]*
No etiology determined 81 (37.2)
Total 218 (100)
* Percent distribution of 167 etiologic agents in 137 patients with CAP.
CAP: Community-acquired pneumonia.
4%-39% for mixed pathogens in different studies (24,28-31). In a previous study from our center, on respiratory tract infections in adults, we de- termined viral antigens and atypical bacterial antigens in 44.4% and 23% of patients, using im- munofluorescence techniques (9). Another study from Turkey reported a level of isolation of atypical agents in CAP of 43.3% (5).
Major identifiable pathogens of CAP include S.
pneumoniae, H. influenzae and atypical patho- gens such as M. pneumoniae, C. pneumoniae and Legionella spp. (1-3). Some studies have identified atypical microorganisms or viruses, more frequently than S. pneumonia. However, the distribution of etiological pathogens of CAP may vary by country and geographical conditi- ons (4). We determined S. pneumoniae as the most frequent pathogen (14.7%) isolated in adult patients with CAP, confirming previous re-
ports from other countries (17,22,25,26,31).
Lim et al. reported S. pneumoniae as a predomi- nant causative agent in nearly half of cases in the UK (17). Again in the UK Creer et al. identi- fied potential pathogens in 69% of patients, and respiratory viruses were the most common ca- use of acute adult lower respiratory tract infecti- ons, occurring in 63% of patients, while bacteria were detected in 26% (16). The latter results dif- fer from those of other studies. The higher pro- portion of viral etiology may be due the use of PCR in that study (16,22).
In the present study, M. pneumoniae was the most frequent atypical pathogen and the second most frequent agent in the etiology of CAP. Some other studies have also reported M. pneumoniae as the most frequent atypical agent (20,24,25,30,32). Cases of atypical pneumonia have increasingly been reported, particularly in studies that have applied highly sensitive diag- Table 3. Distribution of pathogen agents by age.
≥ 65 years, < 65 years,
Microorganism No (%) of cases No (%) of cases p
Etiology determined 61 (64.9) 76 (61.3) 0.586
Typical pathogens 38 (40.4) 40 (32.3) 0.283
Streptococcus pneumoniae 16 (17.0) 16 (12.9) 0.601
Streptococcus spp. 5 (5.3) 0 0.016
Haemophilus influenzae 4 (4.3) 9 (7.3) 0.464
Pseudomonas aeruginosa 4 (4.3) 0 0.037
Moraxella catarrhalis 3 (3.2) 2 (1.6) 0.656
Klebsiella pneumoniae 3 (3.2) 5 (4.0) 1.000
Escherichia coli 0 4 (3.2) 0.130
Other gram-negative 2 (2.1) 2 (1.6) 1.000
Other gram-positive 1 (1.1) 2 (1.6) 1.000
Atypical pathogens 13 (13.8) 31 (25) 0.034
Mycoplasma pneumoniae 8 (8.5) 22 (17.7) 0.052
Chlamydia pneumoniae 4 (4.3) 5 (4.0) 1.000
Legionella pneumophila 1 (1.1) 4 (3.2) 0.384
Viral pathogens 23 (24.5) 22 (17.7) 0.369
Respiratory syncytial virus 13 (13.8) 9 (7.3) 0.205
Parainfluenzae virus 5 (5.3) 6 (4.8) 1.000
Influenzae virus 4 (4.3) 6 (4.8) 1.000
Coxacie virus 1 (1.1) 1 (0.8) 1.000
No etiology determined 33 (35.1) 48 (38.7) 0.586
Total 94 (100) 124 (100)
nostic methods (28). The proportion of atypical pneumonia in other studies has varied from 8% to 63% (2,24,28). Researchers have ascribed this to differences in diagnostic tests, changes in clima- te or the use of different diagnostic criteria (20).
We determined respiratory viral agents in 20.6%
of patients. RSV has been determined as the third most frequent pathogen and the most com- mon viral pathogen at all ages. In patients ≥ 65 it is the second most frequent agent. In recent years, RSV and other respiratory viruses have been detected more often in CAP patients due to use of new diagnostic methods. In different stu- dies the level of respiratory virus has varied from 9% to 63% (16,19,21,24).
L. pneumophila was diagnosed in 2.3% of cases, which agrees with results obtained from previ- ous studies (30). The incidence of Legionella spp. is reported to vary from 0.6% to 12.2% in
sporadic CAP cases. A comprehensive study from Korea reported that L. pneumophila is one of the most common atypical pathogens of CAP around the world (28).
Enterobacteriaceae (E. coli, K. pneumoniae) spp.
and P. aeruginosa rarely cause CAP (30). In our study these pathogens were isolated as the least common microorganisms (1.8%, each).
In our study, mixed pathogens were found in 11.9% of patients. Co-infection rates have been reported in 22.5%, 12.5%, 16%, 8.5% and 5.7%
of CAP in other studies (16,22,24,24,29). Mixed bacterial-viral infections have been increasingly reported in some recent studies. The most com- mon co-pathogens were reported to be S. pne- umoniae, RSV, and parainfluenza virus (17,29).
The detection of mixed pathogens is probably strongly dependent on the diagnostic tests emp- loyed (18).
In CAP, the pattern of causative agents depends on age (33). Fifty-seven percent of the 218 pati- ents in our study were younger than 65. In Tur- key, the 15-64 age group represents 67% of the population (Turkish Statistical Institute, General Population Census and Economic Data, 2009).
While S. pneumoniae was determined at the sa- me rate in both groups, atypical pathogens were found less often in the elderly compared to youn- ger patients. In elderly patients, the most frequ- ent pathogen was S. pneumoniae (17.0%), follo- wed by RSV (13.8%) and M. pneumoniae (8.5%).
Viral pathogens have recently been increasingly diagnosed in elderly patients. In this study, as in others, M. pneumoniae was the most common pathogen in younger patients (30). Lim et al. re- ported atypical pathogen levels of 16% in elderly patients and 27% in younger patients (17).
In this study COPD was the most important co- morbidity. COPD has also been reported as the most common co-morbidity with CAP in other studies (30).
The most important limitation in our study was the small number of CAP patients. Because uni- versity hospitals are tertiary referral centers, and because we excluded all patients who had rece- ived prior antibiotherapy, the number of CAP pa- tients enrolled in this study was inevitably low.
Table 4. Etiological agent detection rates in CAP in Turkey and certain other countries.
Country Etiology (publication year) known % References Turkey (2008) 62.8 Present study
Australia (2008) 45.6 12
Netherlands (2008) 64 13
Asian countries (2008) 44.8 14
Turkey (2007) 21-45.5 5
UK (2007) 69 15
UK (2007) 75 16
Spain (2007) 41.1 17
Spain (2006) 57 18
Japan (2005) 52.8 19
Chile (2003) 55 20
Slovenia (2003) 62.4 21
Thailand (2003) 75.5 22
UK (2001) 75 16
Switzerland (2001) 54.1 23
Taiwan (2001) 59 16
Italy (1999) 44.9 24
France (1994) 72 25
USA (1991) 40 26
Netherlands (1991) 55 26
Israel (1991) 81 26
Finland (1981) 67 26
UK: United Kingdom, USA: United States of America.
In conclusion, a causative pathogen was de- monstrated in 62.8% of patients with CAP. S.
pneumoniae, M. pneumoniae and RSV were the 3 most frequent agents in adults with CAP in an ambulatory setting in this Turkish study. These results suggest that in patients with CAP in initi- al empiric therapy should cover S. pneumoniae and atypical pathogens. Our results showed that in the empirical treatment of CAP suggestions of the Turkish Thoracic Society consensus report are suitable and cover etiological agents of CAP for our country (34).
Conflicts of Interest
None of the authors had any financial or perso- nal relationships with other individuals or orga- nizations that might inappropriately influence their work during the submission process.
ACKNOWLEDGEMENT
1. This study was supported by grants from the Research Foundation of Republic of Turkey Sta- te Planning Organization (Project No:
2003.200.001.1).
2. This study was presented at the 17thEurope- an Congress of Clinical Microbiology and Infec- tious Diseases ICC, Munich, Germany, 31 March - 04 April 2007 (Abstract number: 1733_695).
We would like to thank all our assistant researc- hers and technical personnel for their technical assistance.
REFERENCES
1. Mandell LA. Epidemiology and etiology of community- acquired pneumonia. Infect Dis Clin North Am 2004; 18:
761-76.
2. Lode HM. Managing community-acquired pneumonia: a European perspective. Respir Med 2007; 101: 1864-73.
3. Mandell LA, Wunderink RG, Anzueto A, et al; American Thoracic Society. Infectious Diseases Society of Ameri- ca/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44(Suppl 2): S27-S72.
4. Lagerström F, Bader M, Foldevi M, et al. Microbiological etiology in clinically diagnosed community-acquired pneumonia in primary care in Orebro, Sweden. Clin Mic- robiol Infect 2003; 9: 645-52.
5. Ozlu T, Bulbul Y, Ozsu S. Community-acquired pneumo- nia based on the Turkish national data. Tuberk Toraks 2007; 55: 191-212.
6. Sener B, Tunçkanat F, Ulusoy S, et al. A survey of anti- biotic resistance in Streptococcus pneumoniae and Ha- emophilus influenzae in Turkey, 2004-2005. J Antimic- rob Chemother 2007; 60: 587-93.
7. Honeybourne D. Community-acquired pneumonia in ambulatory patients: relative importance of atypical pat- hogens. Int J Antimicrob Agents 2001; 18: 57-61 8. Ozyilmaz E, Akan OA, Gulhan M, et al. Major bacteria of
community-acquired respiratory tract infections in Tur- key. Jpn J Infect Dis 2005; 58: 50-2.
9. Kaygusuz S, Koksal I, Aydin K, Caylan R. Investigation of atypical bacteria and virus antigens in respiratory tract infections by use of an immunofluorescence met- hod. Jpn J Infect Dis 2004; 57: 33-6.
10. Ozlu T, Bulbul Y, Kaygusuz S, et al. Prevalence of M. pne- umoniae, C. pneumoniae and L. pneumophilia in our ca- ses with community-acquired pneumonia. Solunum Hastalıkları 2000; 11: 135-9.
11. Mandell LA, Wunderink RG, Anzueto A, et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of commu- nity-acquired pneumonia in adults. Clin Infect Dis 2007;
(Suppl 2): 27-72.
12. Lim WS, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentati- on to hospital: an international derivation and validation study. Thorax 2003; 58: 377-82.
13. Charles PG, Whitby M, Fuller AJ, et al. Australian CAP Study Collaboration. The etiology of community-acqu- ired pneumonia in Australia: why penicillin plus doxycycline or a macrolide is the most appropriate the- rapy. Clin Infect Dis 2008; 46: 1522-4.
14. Endeman H, Schelfhout V, Voorn GP, et al. Clinical featu- res predicting failure of pathogen identification in pati- ents with community acquired pneumonia. Scand J In- fect Dis 2008; 8: 1-6.
15. Song JH, Oh WS, Kang CI, et al. Asian Network for Sur- veillance of Resistant Pathogens Study Group. Epidemi- ology and clinical outcomes of community-acquired pneumonia in adult patients in Asian countries: a pros- pective study by the Asian network for surveillance of resistant pathogens. Int J Antimicrob Agents 2008; 31:
107-14.
16. Creer DD, Dilworth JP, Gillespie SH, et al. Aetiological ro- le of viral and bacterial infections in acute adult lower respiratory tract infection (LRTI) in primary care. Thorax 2006; 61: 75-9.
17. Lim WS, Macfarlane JT, Boswell TC, et al. Study of com- munity acquired pneumonia aetiology (SCAPA) in adults admitted to hospital: implications for manage- ment guidelines. Thorax 2001; 56: 296-301.
18. Almirall J, Boixeda R, Bolíbar I, et al; GEMPAC Study Group. Differences in the etiology of community-acqu- ired pneumonia according to site of care: a population- based study. Respir Med 2007; 101: 2168-75.
19. Angeles Marcos M, Camps M, Pumarola T, et al. The role of viruses in the aetiology of community-acquired pne- umonia in adults. Antivir Ther 2006; 11: 351-9.
20. Miyashita N, Fukano H, Mouri K, et al. Community-acqu- ired pneumonia in Japan: a prospective ambulatory and hospitalized patient study. J Med Microbiol 2005; 54:
395-400.
21. Díaz A, Barria P, Niederman M, et al. Etiology of commu- nity-acquired pneumonia in hospitalized patients in Chi- le: the increasing prevalence of respiratory viruses among classic pathogens. Chest 2007; 131: 779-87.
22. Beovic B, Bonac B, Kese D, et al. Aetiology and clinical presentation of mild community-acquired bacterial pne- umonia. Eur J Clin Microbiol Infect Dis 2003; 22: 584-91.
23. Wattanathum A, Chaoprasong C, Nunthapisud P, et al.
Community-acquired pneumonia in southeast Asia the microbial differences between ambulatory and hospitali- zed patients. Chest 2003; 123: 1512-19.
24. Bochud PY, Moser F, Erard P, et al. Community-acquired pneumonia. A prospective outpatient study. Medicine (Baltimore). 2001; 80: 75-87.
25. Logroscino CD, Penza O, Locicero S, et al. Community-ac- quired pneumonia in adults: a multicentric observational AIPO study. Monaldi Arch Chest Dis 1999; 54: 11-7.
26. Moine P, Vercken JB, Chevret S, et al. Severe community- acquired pneumonia. Etiology, epidemiology, and prog- nosis factors. French study group for community-acqu- ired pneumonia in the intensive care unit. Chest 1994;
105: 1487-95.
27. Lauderdale TL, Chang FY, Ben RJ, et al. Etiology of com- munity acquired pneumonia among adult patients requ- iring hospitalization in Taiwan. Respir Med 2005; 99:
1079-86.
28. Sohn JW, Park SC, Choi YH, et al. Atypical pathogens as etiologic agents in hospitalized patients with commu- nity-acquired pneumonia in Korea: a prospective multi- center study. J Korean Med Sci 2006; 21: 602-7.
29. Gutiérrez F, Masiá M, Rodríguez JC, et al. Community-ac- quired pneumonia of mixed etiology: prevalence, clinical characteristics, and outcome. Eur J Clin Microbiol Infect Dis 2005; 24: 377-83.
30. Gutiérrez F, Masiá M, Rodríguez JC, et al. Epidemiology of community-acquired pneumonia in adult patients at the dawn of the 21stcentury: a prospective study on the Mediterranean coast of Spain. Clin Microbiol Infect 2005;
11: 788-800.
31. Howard LS, Sillis M, Pasteur MC, et al. Microbiological profile of community-acquired pneumonia in adults over the last 20 years. J Infect 2005; 50: 107-13
32. Arnold FW, Summersgill JT, Lajoie AS, et al. Commu- nity-acquired pneumonia organization (CAPO) investi- gators. A worldwide perspective of atypical pathogens in community-acquired pneumonia. Am J Respir Crit Care Med 2007; 175: 1086-93
33. Gutiérrez F, Masiá M, Mirete C, et al. The influence of age and gender on the population-based incidence of com- munity-acquired pneumonia caused by different micro- bial pathogens. J Infect 2006; 53: 166-74.
34. Özlü T, Bülbül Y, Alataş F, Arseven O ve ark. Türk Toraks Derneği erişkinlerde toplumda gelişen pnömoni tanı ve te- davi uzlaşı raporu. Turkish Thoracic Journal 2009; Ek 9.
